Tumor-Associated CD68+, CD163+, and MARCO+ Macrophages as Prognostic Biomarkers in Patients With Treatment-Naïve Gastroesophageal Adenocarcinoma

Jeremiasen, Martin; Borg, David; Hedner, Charlotta; Svensson, Marcus; Nodin, Björn; Leandersson, Karin; Johansson, Jan; Jirström, Karin

doi:10.3389/fonc.2020.534761

Cited by 27 publications

(29 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Tumor-infiltrating B cells are closely linked to the tumoral TLS and are considered to be actively involved in the immune response by directing T cell responses to antigens [34,35]. CD68 + TAMs, derived from the innate immune system, are associated with tumor progression and poor survival [36]. Furthermore, our findings showed that a high TLS signature was strongly associated with inflammation-related pathways and immune activation-related pathways.…”

Section: Discussionmentioning

confidence: 58%

The association of immune cell infiltration and prognostic value of tertiary lymphoid structures in gastric cancer

Yu¹,

Huang²,

Zhang³

et al. 2022

neo

View full text Add to dashboard Cite

Tertiary lymphoid structures (TLS) are lymphoid aggregates in tumor tissues and their potential significance in clinical applications has not been fully elucidated in gastric cancer. We evaluated TLS and tumor-infiltrating immune cells using H&E and immunohistochemistry staining in the recruited patients with gastric cancer. The prognostic value of TLS was evaluated by Kaplan-Meier analysis and further validated using gene expression profiling. The alterations in gene mutation, copy number variance, and DNA methylation across the TLS signature subtypes were analyzed based on the Cancer Genome Atlas cohort. High TLS density was associated with improved overall survival and disease-free survival. A combination of TLS density and TNM stage obtained higher prognostic accuracy than the TNM stage alone. Tumors with high TLS density showed significantly higher infiltration of CD3+, CD8+, and CD20+ cells but lower infiltration of CD68+ cells.Transcriptomics analysis demonstrated that high TLS signature status was positively associated with the activation of inflammation-related and immune-related pathways. Multi-omics data showed a distinct landscape of somatic mutations, copy number variants, and DNA methylation across TLS signature subtypes. Our results indicated that TLS might link with enhanced immune responses, and represent an independent and beneficial predictor of resected gastric cancer. Multi-2 omics analysis further revealed key tumor-associated molecular alterations across TLS signature subtypes, which might help explore the potential mechanism of the interaction between TLS formation and cancer cells.

show abstract

Section: Discussionmentioning

confidence: 58%

The association of immune cell infiltration and prognostic value of tertiary lymphoid structures in gastric cancer

Yu¹,

Huang²,

Zhang³

et al. 2022

neo

View full text Add to dashboard Cite

show abstract

“…Only one study that assessed PET imaging with specific tracers for inflammation in a small group of vestibular schwannomas shown a higher cell density in non-growing tumors compared to growing VS [ 9 ]. The immunohistochemical markers CD68 and CD163 for the detection of tumor-associated macrophages are widely used [ 20 , 21 ]. However, the quantification of immunohistochemistry of macrophage markers is not standardized, and divergent results can be explained by technical limitations and antibody employment [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Macrophage and Lymphocyte Infiltration Is Associated with Volumetric Tumor Size but Not with Volumetric Growth in the Tübingen Schwannoma Cohort

Gonçalves

Suhm

Ries

et al. 2021

Cancers

View full text Add to dashboard Cite

Most patients with vestibular schwannomas can be cured with microsurgical resection, or tumor growth can be stabilized by radiotherapy in certain cases. Recurrence is rare but usually difficult to treat. Treatment alternatives to local therapies are not established. There is growing evidence of the role of inflammatory processes in schwannomas, which may be exploitable by targeted innovative therapies. To further define the impact of inflammation with tumor growth in vestibular schwannoma, we performed immunohistochemical analyses of CD3, CD8, CD68 and CD163 to assess lymphocyte and macrophage infiltration in 923 tumor tissue samples of surgically resected vestibular schwannomas. An inflammatory score was compared with tumor size and volumetric growth. We observed a significantly larger preoperative tumor size with increased expression rates of CD3, CD8, CD68 and CD163 (p < 0.0001, p < 0.0001, p = 0.0015 and p < 0.0001, respectively), but no differences in percentual volumetric tumor growth. When all four markers were combined as an inflammatory score, tumors with high inflammatory infiltration showed slower percentual growth in a multivariate analysis, including MIB1 expression (p = 0.0249). We conclude that inflammatory cell infiltration increases with larger tumor size but is associated with slower percentual volumetric tumor growth.

show abstract

“…There are also contrasting prognostic effects of the Foxp3/CD4 ratio in CGC and NCGC (25), which suggests that location may be an important factor for tumor progression. It is possible that neglecting the location during risk assessment could account for the differential findings in previous studies (26,27). Indeed, accumulating evidence has demonstrated distinct molecular a nd patho physi ologic al me chanisms of carcinogenesis in CGC and NCGC (28,29).…”

Section: Discussionmentioning

confidence: 95%

The Distinct Impact of TAM Infiltration on the Prognosis of Patients With Cardia and Non-Cardia Gastric Cancer and Its Association With H. pylori Infection

et al. 2021

View full text Add to dashboard Cite

BackgroundIn stage III gastric cancer (GC), the role of tumor-associated macrophages (TAMs) and Helicobacter pylori (H. pylori) infection impact tumor progression; however, the specific mechanisms remain controversial. We speculated whether this controversy is caused by differences in the location of TAM infiltration (in the core (CT) and invasive margin (MI) of primary tumors) and the topographical subsites of GC (cardia and non-cardia). Therefore, in this study, we investigated TAMs in different locations and H. pylori infection status as prognostic biomarkers for GC.MethodsImmunohistochemical staining for CD68 (pan-macrophage), CD163 (M2-like macrophage), and H. pylori in 200 samples (100 cases of cardia-GC [CGC] and 100 cases of non-cardia GC [NCGC]) was performed. We compared the number of CD68+ and CD163+ macrophages that infiltrated the CT and MI in patients with the prognosis of CGC and NCGC, respectively. In addition, we analyzed the relationship between H. pylori status and the prognosis of patients with GC in different locations, as well as the correlation with TAM infiltration.ResultsThe distribution of TAMs had distinct characteristics in CGC and NCGC, especially differences between CT and MI subtype. A Kaplan–Meier analysis showed that a high number of CD68+ macrophages that infiltrated the CT in CGC was associated with a better prognosis, whereas infiltration at the MI in NCGC indicated a poor prognosis. Furthermore, a high number of CD163+ macrophages infiltrating the MI resulted in a poor prognosis in CGC and NCGC cohorts. Considering the larger differences in the relationship between the infiltration of CD68+ macrophages at different locations and prognosis, we divided the GC cases into marginal and central GC, based on this difference. This resulted in an accurate estimation of the prognosis. Moreover, positive H. pylori status in central GC was significantly associated with a better prognosis and TAM infiltration.ConclusionTAMs in different locations and H. pylori status were identified as independent prognostic markers, with an obvious correlation between them. Therefore, it is important to clarify the impact of TAM location on the prognosis of patients with GC, which contributes to the development of potential therapeutic strategies.

show abstract

Tumor-Associated CD68+, CD163+, and MARCO+ Macrophages as Prognostic Biomarkers in Patients With Treatment-Naïve Gastroesophageal Adenocarcinoma

Cited by 27 publications

References 26 publications

The association of immune cell infiltration and prognostic value of tertiary lymphoid structures in gastric cancer

The association of immune cell infiltration and prognostic value of tertiary lymphoid structures in gastric cancer

Macrophage and Lymphocyte Infiltration Is Associated with Volumetric Tumor Size but Not with Volumetric Growth in the Tübingen Schwannoma Cohort

The Distinct Impact of TAM Infiltration on the Prognosis of Patients With Cardia and Non-Cardia Gastric Cancer and Its Association With H. pylori Infection

Contact Info

Product

Resources

About